| 1. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 2. |
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| 3. |
- Düzel, E., et al.
(författare)
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European Ultrahigh-Field Imaging Network for Neurodegenerative Diseases (EUFIND)
- 2019
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Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - : Wiley. - 2352-8729. ; 11, s. 538-549
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The goal of European Ultrahigh-Field Imaging Network in Neurodegenerative Diseases (EUFIND) is to identify opportunities and challenges of 7 Tesla (7T) MRI for clinical and research applications in neurodegeneration. EUFIND comprises 22 European and one US site, including over 50 MRI and dementia experts as well as neuroscientists. Methods: EUFIND combined consensus workshops and data sharing for multisite analysis, focusing on 7 core topics: clinical applications/clinical research, highest resolution anatomy, functional imaging, vascular systems/vascular pathology, iron mapping and neuropathology detection, spectroscopy, and quality assurance. Across these topics, EUFIND considered standard operating procedures, safety, and multivendor harmonization. Results: The clinical and research opportunities and challenges of 7T MRI in each subtopic are set out as a roadmap. Specific MRI sequences for each subtopic were implemented in a pilot study presented in this report. Results show that a large multisite 7T imaging network with highly advanced and harmonized imaging sequences is feasible and may enable future multicentre ultrahigh-field MRI studies and clinical trials. Discussion: The EUFIND network can be a major driver for advancing clinical neuroimaging research using 7T and for identifying use-cases for clinical applications in neurodegeneration. © 2018 The Authors
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| 4. |
- Bowtell, J. L., et al.
(författare)
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Short Duration Small Sided Football and to a Lesser Extent Whole Body Vibration Exercise Induce Acute Changes in Markers of Bone Turnover
- 2016
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Ingår i: Biomed Research International. - : Hindawi Limited. - 2314-6133 .- 2314-6141.
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to study whether short-duration vibration exercise or football sessions of two different durations acutely changed plasma markers of bone turnover and muscle strain. Inactive premenopausal women (n = 56) were randomized to complete a single bout of short (FG15) or long duration (FG60) small sided football or low magnitude whole body vibration training (VIB). Procollagen type 1 amino-terminal propeptide (P1NP) was increased during exercise for FG15 (51.6 +/- 23.0 to 56.5 +/- 22.5 mu g.L-1, mean +/- SD, P < 0.05) and FG60 (42.6 +/- 11.8 to 50.2 +/- 12.8 mu g.L-1, P < 0.05) but not for VIB (38.8 +/- 15.1 to 36.6 +/- 14.7 mu g.L-1, P > 0.05). An increase in osteocalcin was observed 48 h after exercise (P < 0.05), which did not differ between exercise groups. C-terminal telopeptide of type 1 collagen was not affected by exercise. Blood lactate concentration increased during exercise for FG15 (0.6 +/- 0.2 to 3.4 +/- 1.2mM) and FG60 (0.6 +/- 0.2 to 3.3 +/- 2.0 mM), but not for VIB (0.6 +/- 0.2 to 0.8 +/- 0.4mM) (P < 0.05). Plasma creatine kinase increased by 55 +/- 63% and 137 +/- 119% 48 h after FG15 and FG60 (P < 0.05), but not after VIB (26 +/- 54%, NS). In contrast to the minor elevation in osteocalcin in response to a single session of vibration exercise, both short and longer durations of small sided football acutely increased plasma P1NP, osteocalcin, and creatine kinase. This may contribute to favorable effects of chronic training on musculoskeletal health.
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| 5. |
- Bowtell, J. L., et al.
(författare)
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Improved Exercise Tolerance with Caffeine Is Associated with Modulation of both Peripheral and Central Neural Processes in Human Participants
- 2018
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Ingår i: Frontiers in Nutrition. - : Frontiers Media SA. - 2296-861X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Caffeine has been shown to enhance exercise performance and capacity. The mechanisms remain unclear but are suggested to relate to adenosine receptor antagonism, resulting in increased central motor drive, reduced perception of effort, and altered peripheral processes such as enhanced calcium handling and extracellular potassium regulation. Our aims were to investigate how caffeine (i) affects knee extensor PCr kinetics and pH during repeated sets of single-leg knee extensor exercise to task failure and (ii) modulates the interplay between central and peripheral neural processes. We hypothesized that the caffeine-induced extension of exercise capacity during repeated sets of exercise would occur despite greater disturbance of the muscle milieu due to enhanced peripheral and corticospinal excitatory output, central motor drive, and muscle contractility. Methods: Nine healthy active young men performed five sets of intense single-leg knee extensor exercise to task failure on four separate occasions: for two visits (6 mg.kg(-1) caffeine vs placebo), quadriceps P-31-magnetic resonance spectroscopy scans were performed to quantify phosphocreatine kinetics and pH, and for the remaining two visits (6 mg.kg-1 caffeine vs placebo), femoral nerve electrical and transcranial magnetic stimulation of the quadriceps cortical motor area were applied pre- and post exercise. Results: The total exercise time was 17.9 +/- 6.0% longer in the caffeine (1,225 +/- 86 s) than in the placebo trial (1,049 +/- 73 s, p = 0.016), and muscle phosphocreatine concentration and pH (p < 0.05) were significantly lower in the latter sets of exercise after caffeine ingestion. Voluntary activation (VA) (peripheral, p = 0.007; but not supraspinal, p = 0.074), motor-evoked potential (MEP) amplitude (p = 0.007), and contractility (contraction time, p = 0.009; and relaxation rate, p = 0.003) were significantly higher after caffeine consumption, but at task failure MEP amplitude and VA were not different from placebo. Caffeine prevented the reduction in M-wave amplitude that occurred at task failure (p = 0.039). Conclusion: Caffeine supplementation improved high-intensity exercise tolerance despite greater-end exercise knee extensor phosphocreatine depletion and H+ accumulation. Caffeine-induced increases in central motor drive and corticospinal excitability were attenuated at task failure. This may have been induced by the afferent feedback of the greater disturbance of the muscle milieu, resulting in a stronger inhibitory input to the spinal and supraspinal motor neurons. However, causality needs to be established through further experiments.
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